Genes and kicking the habit

Genes contribute to withdrawal symptoms as smokers try to quit

Researchers at Washington University School of Medicine in St. Louis have uncovered evidence linking genetic influences to nicotine withdrawal symptoms that commonly occur when a smoker attempts to stop smoking.

Their findings, published in the March 2003 issue of the journal Nicotine and Tobacco Research, also indicate that genetic factors both related and unrelated to nicotine withdrawal may affect attempts to quit smoking. While genetic influences accounted for 54 percent of failures to quit smoking, about one-third of such influences were attributed to the severity of symptoms of nicotine withdrawal.

Genetic factors influence nicotine withdrawal symptoms and make it difficult for some smokers to quit.

“Many people who try to quit smoking restart within a week and about 90 percent relapse within a year,” says Hong Xian, Ph.D., research assistant professor of medicine at Washington University School of Medicine and researcher at the St. Louis Veterans Affairs Medical Center. “We wanted to learn why these smokers have such a difficult time trying to quit.”

Xian’s study does not identify specific genes that might be involved in nicotine withdrawal, but it may represent an important step in the development of future smoking cessation therapies. Because Xian and second author Jeffery Scherrer of St. Louis University School of Public Health, and other colleagues in Washington University’s Department of Psychiatry and at Harvard University have determined that genetic factors are involved in nicotine withdrawal, it might someday be possible to target genes associated with the problem, thereby improving a smoker’s odds of quitting.

At the same time, the study confirmed that genes don’t tell the whole story. Environmental factors also play a significant role in determining a person’s success in quitting.

Xian and his colleagues studied twins to evaluate three factors that could influence addiction: genetics, shared environmental factors and unique environmental factors.

Hong Xian, Ph.D.

The data came from the Vietnam Era Twin Registry, a large, nationwide pool of physical and behavioral information drawn from 4,000 pairs of male twins — identical, fraternal and singletons (that is, a twin whose co-twin could not be reached for questioning) —who served in the military between 1965 and 1975. Information about cigarette consumption was obtained from follow-up telephone interviews that included questions about smoking habits. The researchers measured the contribution of genetic factors by comparing sets of identical twins, who share exactly the same genes, to fraternal twins, who are no more genetically similar than other siblings.

Shared environmental factors address experiences shared by twin siblings — being reared by the same parents, living in the same neighborhood, going to the same school — that might influence both identical and fraternal twins. By the process of elimination, unique environmental factors — that is, non-shared experiences — account for any remaining influences.

Xian and colleagues studied more than 1,800 pairs of twins who were lifetime smokers where both twin siblings had attempted to quit at least once. The twins were asked whether they had ever experienced any of 12 symptoms of nicotine withdrawal, ranging from restlessness and anxiety to headache and nausea.

Using statistical analysis, the researchers then calculated the odds of a failed attempt to quit smoking based on individual symptoms. Then they computed a single variable that captured both the overall severity of nicotine withdrawal and number of symptoms, and they used that variable to create a model evaluating the association between nicotine withdrawal symptoms and failure in attempts to quit smoking.

By comparing the groups of identical versus fraternal twins, the researchers were able to formulate conclusions about the degree to which genes contributed to the results.

Somewhat surprisingly, results were statistically equivalent whether or not shared environmental factors were included. The researchers determined that shared environmental factors did not significantly contribute to either failed attempts to quit smoking or to nicotine withdrawal, so they eliminated them from their final results.

But unique environmental factors seemed very important in determining a person’s odds of quitting. For example, a person whose friends are smokers might have a more difficult time than a person whose friends don’t smoke. On the other hand, someone with a close friend or family member who recently suffered from a smoking related illness, such as lung cancer, might have an extra incentive to stop smoking.

“Just because genes influence failed smoking cessation and nicotine withdrawal, it doesn’t mean that we can’t influence our own choices,” concludes Xian. “People still have free will and still can stop smoking, even if their genetic make-up might make it very difficult.”

But genetic factors correlate strongly with symptoms of withdrawal, and the various symptoms that smokers develop when they attempt to quit go a long way toward determining whether their attempt will be successful. Xian says recently developed drugs help many people quit by alleviating some of the discomfort that smokers experience during withdrawal. But he believes as the genetic picture becomes clearer, it may be possible to target the genes associated with nicotine withdrawal and match drug therapies to individual smokers trying to quit.